Targeted deletion of neuropeptide Y (NPY) modulates experimental colitis

Bindu Chandrasekharan, Vanitha Bala, Vasantha L. Kolachala, Matam Vijay-Kumar, Dean Jones, Andrew T. Gewirtz, Shanthi V. Sitaraman, Shanthi Srinivasan

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Abstract

Background: Neurogenic inflammation plays a major role in the pathogenesis of inflammatory bowel disease (IBD). We examined the role of neuropeptide Y (NPY) and neuronal nitric oxide synthase (nNOS) in modulating colitis. Methods: Colitis was induced by administration of dextran sodium sulphate (396 DSS) or streptomycin pre-treated Salmonella typhimurium (S.T.) in wild type (WT) and NPY (NPY-/-) knockout mice, Colitis was assessed by clinical score, histoligical score and myelopexidase activity. NPY and nNOS expression was assessed by immunostaining. Oxidative stress was assessed by measuring catalase activity, glutathione and nitrite levels. Colonic motility was assessed by isometric muscle recording in WT and DS-treated mice. Results: DSS/S.T. induced an increase in enteric neuronal NPY and nNOS expression in WT mice. WT mice were more susceptible to inflammation compared to NPY-/- as indicating higher clinical & histological cores, and myeloperoxide (MPO) activity (p<0.01). DSS-WT mice had increased nitrite, decreased glutathione(GSH) levels and increased catalase activity indicating more oxidative stress. The lower histoligical scores, MPO and chemokin KC in S.T.-treated nNOS-1- and NPY-/-/nNos-/- mice supported the findings loss of of NPY-induced nNOS attenuated inflammation. The inflammation resulted in chronic impairment of colonic in DSS-WT mic. NPY -treated rat enteric neuronsin vetro exhibited increased nitrite and TNF-α production. Conclusions: NPY mediated increase in nNOS is a determinant of oxidative stress and subsequent inflammation. Our study highlights the role of neuronal NPY and nNOS as mediators of inflammatory processes in IBD.

Original languageEnglish (US)
Article numbere3304
JournalPloS one
Volume3
Issue number10
DOIs
StatePublished - Oct 1 2008

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Chandrasekharan, B., Bala, V., Kolachala, V. L., Vijay-Kumar, M., Jones, D., Gewirtz, A. T., Sitaraman, S. V., & Srinivasan, S. (2008). Targeted deletion of neuropeptide Y (NPY) modulates experimental colitis. PloS one, 3(10), [e3304]. https://doi.org/10.1371/journal.pone.0003304